(568c) Development and Scale-up of a Crystallization Process for a Kinetically-Unfavorable Polymorph

ABSTRACT: This work describes the development and scale-up of a crystallization process to isolate a thermodynamically stable but kinetically unfavorable polymorph of a small organic agrochemical prone to oiling. The process involves simultaneous addition of solution and antisolvent into a slurry of the desired polymorph, similar to semi-batch, reverse addition antisolvent crystallization.[1] For this system, the simultaneous addition process is more robust to feed variation than a traditional antisolvent process and affords suitable polymorph control, recovery, cycle time, and purity. However, the process produces a thick, but shear-thinning slurry of fine, needle-like particles that is challenging to mix well. Mixing analysis tools, including both the Fluid Mixing Processes (FMP) Excel Design Guide and computational fluid dynamics simulations were utilized to enable successful scale-up of this mixing-sensitive process from lab to pilot plant.

[1] R. Pena, C.L. Burcham, D.J. Jarmer, D. Ramkrishna, Z.K. Nagy, “Modeling and optimization of spherical agglomeration in suspension through a coupled population balance model,” Chemical Engineering Science, 167 pp. 66-77, 2017.